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PRCTICA I.2
DETERMINAO DE CONSTANTES
HIDROFBICAS DE SUBSTITUINTES DE
SULFONAMIDAS POR MEIO DE
CROMATOGRAFIA EM CAMADA DELGADA EM
FASE REVERSA
DETERMINATION OF HYDROPHOBIC
CONSTANTS OF SULFONAMIDE
SUBSTITUENTS BY REVERSED-PHASE THINLAYER CHROMATOGRAPHY
Maria Auxiliadra Fontes Prado
Laboratrio de Qumica Farmacutica, Departamento de Produtos
Farmacuticos, Faculdade de Farmcia, Universidade Federal de
Minas Gerais, Av. Olegrio Maciel, 2360-31180-112, Belo Horizonte,
Brasil
E-mail: doraprad@dedalus.lcc.ufmg.br
INTRODUO
A relao entre a estrutura qumica e atividade atividade biolgica (REA, SAR) das
substncias pode ser determinada de maneira qualitativa. O estudo da relao entre
estrutura e atividade pode ser feito tambm de maneira quantitativa (REAQ, QSAR),
sendo que neste caso, os efeitos eletrnicos (, estereoqumicos (Es) e de solubilidade
() dos grupos funcionais (substituintes) presentes na estrutura do frmaco so medidos
e relacionados atividade por meio de modelos matemticos. Estudos de QSAR
possibilitam explicar de forma quantitativa a relao entre a estrutura qumica e
atividade biolgica e planejar modificaes moleculares de forma a se obter frmacos
com vantagens sobre o prottipo.
De todos os parmetros fsico-qumicos, o coeficiente de partio (P) tem sido o mais
utilizado nos estudos de QSAR, uma vez que este parmetro influencia, efetivamente,
nas propriedades farmacocinticas e permite avaliar a possibilidade de formao de
ligaes hidrofbicas com os receptores. A contribuio dos diversos substituintes na
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x = log
PRX
= log PRX log PRH
PRH
x = Rm RX Rm RH
O valor de Rm calculado com base no valor de Rf em cromatografia em camada
delgada em fase reversa (fase estacionria hidrofbica, fase mvel polar; as substncias
menos polares interagem mais efetivamente com a fase estacionria, portanto, as
substncias menos polares permanecem mais retidas, apresentando Rf menor que as
mais polares), utilizando a seguinte expresso:
1
Rm = log
1
Rf
[ ]
[ ]
Ka + H +
1
1 + log
Rm = log
H+
Rf
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2
NH2
R= H
sulfanilamida 1
pKa= 10,45
OCH3
R=
N
sulfametoxipiridazina 3
pKa= 7,05
CH3
S
R=
N
sulfatiazol 2
pKa= 7,10
sulfametazina 4
R=
pKa= 7,70
CH3
TCNICA
CLCULOS
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3
REFERNCIAS
1.
2.
3.
trabalho
em
laboratrios
de
Qumica
Medicinal
requer
vidrarias
de
solventes
no
representam
problemas
documento
foi
supervisionado
pelo
Prof.
Maria
sobre
realizao
inexistncia
deste
de
riscos
exerccio
especficos
(e.g.,
na
toxicidade,
execuo
de
toda
qualquer
prtica
em
Se
seu
exerccio
ou
prtica
envolver
qualquer
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4
risco
EXERCISE I.2
DETERMINATION OF LIPOPHILICITY
SUBSTITUENT CONSTANTS OF
SULFONAMIDES BY MEANS OF REVERSEDPHASE THIN-LAYER CHROMATOGRAPHY
Maria Auxiliadra Fontes Prado
Laboratrio de Qumica Farmacutica, Departamento de Produtos
Farmacuticos, Faculdade de Farmcia, Universidade Federal de
Minas Gerais, Av. Olegrio Maciel, 2360-31180-112, Belo Horizonte,
Brasil
E-mail: doraprad@dedalus.lcc.ufmg.br
INTRODUCTION
The partition coefficient (P) is one of the most important factors in controlling drug
action in biological systems. Hansch and coworkers [1] derived substituent constants for
the contribution of individual atoms or groups to the partition coefficient, the
lipophilicity (or hydrophobicity, or Hansch) constant (). This is defined as the log PRX
log PRH (eq. 1), where PRX and PRH are the partition coefficients, determined in
system 1-octanol-water, of substituted and unsubstituted compounds, respectively.
Thus, the constant indicates the change in the logarithm of the partition coefficient
resulting from the introduction of a substituent X.
x = log
PRX
= log PRX log PRH
PRH
Rm = log
1
Rf
(2)
[ ]
[ ]
Ka + H +
1
1 + log
Rm = log
Rf
H+
(3)
x = Rm RX Rm RH
(4)
R= H
NH2
sulfanilamide
pKa= 10,45
OCH3
R=
N N
S
sulfathiazole pKa= 7,10
R=
O S
N R
O H
CH3
N
R=
sulfamethazine
pKa= 7,70
N
CH3
EXPERIMENTAL
Stationary phase: Mix 6 g of silica gel with 15 mL of water, shake, coat the plates
(12 glass plates measuring 9 4.5 cm; 0.25 mm), dry at room temperature, heat in
oven at 120 C for 4 h, and cool at room temperature. A stationary nonpolar phase is
obtained by impregnation of the silica gel layer with a 5 % 1-octanol in ethyl ether.
The impregnation is carried out by immersion of the plates in the solution. The silica
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gel layer is removed at 3 mm from each lateral edge and 1 cm from the high edge.
Mobile phase: An aqueous buffer at pH 7.4 (mixture of 50 mL of 0.1 mol/L
potassium dihydrogen phosphate solution and 19.5 mL of 0.1 mol/L sodium
hydroxide solution).
Samples: The sulfonamides (sulfanilamide, sulfathiazole, sulfamethazine, and
sulfamethoxypyridazine) are dissolved in acetone (10 mg in 25 mL).
Chromatography: The solutions of sulfonamides are spotted on a line 1 cm from the
lower edge of the plate using a glass capillary. The plate is left in the
chromatographic chamber until the mobile phase reaches the end of the stationary
layer.
Revelation: The developed plate is dried with hot air, and the spots appear by
spraying the plate with a solution prepared by adding 1 mL of concentrated
hydrochloridric acid to 100 mL of 0.1 % p-dimethylaminebenzaldehyde solution in
ethanol.
CALCULATIONS
REFERENCES
1.
2.
3.
materials,
dissolvents
and
other
inflammable
This
document
has
been
supervised
by
Prof.
Maria
(regarding
toxicity,
inflammability,
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explosions),
If
your
exercise
involves
any
special
risks,
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please